Synthetases, polymerases and ATPases are being studied with a combination of oxygen-labeling and stereochemical techniques. Alpha-Thiophosphate analo ues of ATP colled the ATP (alpha-thiophosphate) "A" and "B" stereo isomers, were synthesized and separated to study the stereochemical course of yeast acetyl CoA synthetase. This enzyme was shown to proceed with inversion of configuration at the alpha-thiophosphate center (J. Biol. Chem., Oct. 25, 1978). A number of amino acyl tRNA synthetases from E. Coli B have been found to have acceptable activity toward "A" or "B" ATP (alpha S), specifically the lysyl, phenylalamyl, histidyl cysteinyl and methionyl tRNA synthetases. The stereochemical consequences of the amino acid activation step in these systems are presently being studies. The alpha-thiophosphate analogues of TTP have been synthesized and separated. They have excellent substrate activity in several polymerase reactions tested so far including the E. Coli polymerase 1, and HeLa cell alpha, Beta and gamma polymerases. The specificity of snake venom phoaphodiesterase toward one dieterase isomer is being used to investigate the structure of the product DNA polymer. Myosin ATPase was studied in collaboration with Dr. David Trentham of the University of Pennsylvania. The mechanism of the ATP yields (reversibly) H2O oxygen exchange was shown to involve the reversible cleavage of ATP to ADP plus Pi by starting with 180-ATP specifically labeled in certain of the phosphate oxygens of the ATP.